This invention generally relates to immobilized anti-ligands, and more particularly relates to a solid support having immobilized anti-ligands thereon, which is useful as a sample array holder in generating information in analog form about multianalytes of interest, and which further carries information in digital form related to the multianalyte detection on the same support. Preferred solid support embodiments have miniaturized quantities of reagents, on one side (e.g. a microarray), and can be used in powerful analytical techniques such as matrix assisted laser desorption/ionization mass spectrometry, as part of a microfraction collector, as an auto sampler, and for incorporation into a micro-robotic platform system.
Clinical and diagnostic assays can be relatively expensive to perform, involve wasted reagents (e.g. patient blood), and are limited in the number of multianalytes run. Particularly where one wishes to perform a large number of assays, such as for environmental monitoring, the present tools for conducting these analyses have posed problems of cost and inefficiencies.
Further, although mass spectrometry has been used for the analysis of molecules for over 50 years, its application to large biomolecules and synthetic polymers has been limited due to various problems.
Antibody immobilization on thin-layer immunoaffinity chromatography membranes through use of a modified piezoelectric driven ink-jet printer has recently been reported by Nilsson et al. in Analytical Chemistry, 67, pages 3051-3056 (1995). These immobilized antibodies can be in the form of several bands with different amounts of antibodies for quantitative measurement of the antigen of interest.
Ekins and Chu in U.S. Pat. No. 5,516,635, issued May 14, 1996, describe a solid support with microspots with which labeled microspheres are used to perform immunoassays. The strength of signal from the labels is representative of the fractional occupancy of binding sites.
U.S. Pat. No. 5,494,829, issued Feb. 27, 1996, Sandstrom et al., and U.S. Pat. No. 5,552,272, issued Sep. 3, 1996, Bogart, describe optical supports which are said to have an enhanced level of exciting photons to immobilize fluorescent labels. The optical substrates produce different colors related to the thickness of a film.
In addition to the well established chemical analysis methods such as ELISA, a number of chromatographic and spectral analytical techniques have been more recently developed. A powerful new technique, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), has overcome some of the mass spectrometry problems encountered, particularly when applied to large biomolecules and synthetic polymers, as the technique permits the mass analysis of high molecular weight biopolymers. The technique is based upon an ultraviolet absorbing matrix pioneered by Karas and Hillencamp, Analytical Chemistry, 60, p. 2301 (1988).
Thus, advances in the technology for immobilization of reagents, particularly through miniaturization and increased automation of detection, are being made. Nevertheless, a need remains for highly automated assay devices and sample array holders, useful for environmental monitoring, clinical screening, and the like, so as to perform analyses efficiently at reasonable cost.
In one aspect of the present invention, a solid support is provided that has at least one capture binding agent on a support surface. The support surface also includes areas adapted to be digitally readable by laser when information is carried thereon. In addition or as an alternative, these informational areas are adapted to be digitally writable by laser so as to carry selected information thereon. Such information is preferably carried via a plurality of microscopic pit and land formations. In use, the inventive supports can store information concerning binding between capture binding agents and analytes.
Particularly preferred support embodiments of the invention are optical compact discs that carry specific reagents capable of binding with multiple analytes. The specific reagents, or capture binding agents, are preferably immobilized on the discs by means of a computer controlled, miniaturized printing system. These support embodiments are useful in conducting chemical reactions to detect analytes of interest and to read and/or store electronic information, for example, electronic information that records the assay results, on the support itself by use of a laser.
The support embodiments are particularly useful as sample array holders in performing chemical analyses such as in performing matrix assisted laser desorption/ionization time-of-flight mass spectrometry analyses where the capture binding agents are admixed with matrix.
In another aspect of the present invention, an apparatus is provided that comprises at least one piezoelectric head contained in a commercially available printhead of an ink jet printer. The printhead is removed from the printer and fixed on a disk drive""s carriage sliding mechanism while remaining connected to the printer""s printhead driver circuitry via a printer ribbon cable. Both the platter and sliding mechanism on the floppy disk drive assembly are controlled by a program via a digital interface card in the ISA port of the personal computer. By controlling the disk drive""s carriage sliding mechanism, the piezoelectric head can be positioned at any specific position over the support surface to apply droplets of reagents on the support surface.
In another aspect of the present invention, the printhead comprises a plurality of piezoelectric heads. Each of the piezoelectric heads connects to a separate syringe cylinder containing a different reagent to be printed on the support surface. Therefore, a combination of different reagents can be applied to any position on the support surface.